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Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans
Open accessAbstract
During C. elegans development, the temporal pattern of many cell lineages is specified by graded activity of the heterochronic gene Lin-14. Here we demonstrate that a temporal gradient in Lin-14 protein is generated posttranscriptionally by multiple elements in the lin-14 3'UTR that are regulated by the heterochronic gene Lin-4. The lin-14 3'UTR is both necessary and sufficient to confer lin-4-mediated posttranscriptional temporal regulation. The function of the lin-14 3'UTR is conserved between C. elegans and C. briggsae. Among the conserved sequences are seven elements that are each complementary to the lin-4 RNAs. A reporter gene bearing three of these elements shows partial temporal gradient activity. These data suggest a molecular mechanism for Lin-14p temporal gradient formation: the lin-4 RNAs base pair to sites in the lin-14 3'UTR to form multiple RNA duplexes that down-regulate lin-14 translation.
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“MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression and thus act as important regulators of cellular phenotype and function.”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [2]
In the citing paper
“Two C. elegans miRNAs, lin-4 and let-7, control developmental timing by forming imperfect base pairing with elements within the 3Ј UTR of target mRNAs and attenuating their translation (Lee et al. 1993;Wightman et al. 1993;Olsen and Ambros 1999;Reinhart et al. 2000;Slack et al. 2000).”
From A microRNA array reveals extensive regulation of microRNAs during brain development (2003) · cites this paper as Wightman et al. 1993
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Metadata
- Authors
- Wightman, B., Ha, I., & Ruvkun, G.
- Affiliations
- Massachusetts General Hospital (US)
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1993-12
- Volume
- 75
- Issue
- 5
- Pages
- 855-862
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2160467221
- Cited by
- 4,292
- References
- 27
- Citations by year
- 2026: 86 · 2025: 189 · 2024: 151 · 2023: 164 · 2022: 171 · 2021: 193 · 2020: 177 · 2019: 172 · 2018: 189 · 2017: 235 · 2016: 193 · 2015: 227 · 2014: 224 · 2013: 281 · 2012: 231
- FWCI
- 6.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM44619, R01GM044619)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- lin-14, lin-4, post-transcriptional regulation, 3' untranslated region, heterochronic genes, RNA duplex, protein synthesis inhibition, Caenorhabditis elegans, Caenorhabditis briggsae, developmental timing, cell lineage specification
- MeSH terms
- Animals, Base Sequence, Caenorhabditis, Gene Expression Regulation, Molecular Sequence Data, Morphogenesis, RNA, Messenger, Sequence Homology, Nucleic Acid, Species Specificity, Time Factors, Protein Biosynthesis, Helminth Proteins, RNA, Antisense, Sequence Alignment, Genes, Helminth
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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